Exaggerated discharges of the sympathetic nervous system which occur during morphine withdrawal produce many of the characteristic clinical signs including hypertension and tachycardia. It recently has been observed that clonidine, a non-opiate antihypertensive agent, reduced the symptoms of the abstinence syndrome in morphine-dependent patients. The central mechanism through which clonidine produces this effect is unknown, however, recent studies by the author have demonstrated that this drug inhibits the release of acetylcholine from central cholinergic neurones. This finding is important in view of the fact that stimulation of central cholinergic neurones in experimental animals and humans produces symptoms similar to those of narcotic withdrawal. In the present study experiments have been designed to determine whether clonidine's anti-withdrawal actions are related to its ability to inhibit the function of central cholinergic neurones. Rats made physically dependent on morphine will be withdrawn from the drug, and arterial blood pressure will be monitored continuously as a direct index of sympathetic activity. Since these animals will be freely-moving during this procedure, several behavioral parameters of withdrawal also will be measured. Clonidine's anti-withdrawal effects then will be ascertained and related to its ability to alter the metabolism of regional brain acetylcholine. Also, other drugs which alter brain cholinergic function will be examined for their ability to alter the autonomic or behavioral signs of withdrawal. The results of this study should aid in the development of a new approach to the pharmacologic treatment of narcotic withdrawal symptoms.